ROLE OF NEUTROPHIL DERIVED OXIDANTS AND ELASTASE IN LIPOPOLYSACCHARIDE-MEDIATED RENAL INJURY

被引:40
作者
LINAS, SL [1 ]
WHITTENBURG, D [1 ]
REPINE, JE [1 ]
机构
[1] UNIV COLORADO, HLTH SCI CTR, WEBB WARING LUNG INST, DENVER, CO 80262 USA
关键词
D O I
10.1038/ki.1991.73
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Gram-negative bacterial sepsis is frequently associated with acute renal failure but the specific effects of lipopolysaccharide (LPS) and other bacterial products on kidney function are not known. Since either LPS or formyl-methionyl-leucyl-phenylalanine (FMLP)-a chemotactic peptide from bacterial cell walls-activate neutrophils (PMN) to release a number of potentially toxic factors in vitro, we determined the effect of adding PMN with LPS and/or FMLP to isolated perfused rat kidneys. Isolated rat kidneys perfused with LPS alone of LPS and normal PMN had normal glomerular filtration rates (GFR) and tubular Na reabsorption (T(Na)). Kidneys perfused with FMLP alone or FMLP and normal PMN also had normal GFR and T(Na). In contrast, addition of PMN with both FMLP and LPS caused progressive renal dysfunction. For example, after 60 minutes of perfusion, GFR was reduced from 610 +/- 31 to 147 +/- 17-mu-l/min/g and T(Na) from 97 +/- 1 to 72 +/- 2%, both P < 0.01. Perfusion with the O2 metabolite scavengers catalase or dimethylthiourea afforded no protection while perfusion with the neutrophil elastase inhibitor Eglin C conferred substantial, but not complete, protection: GFR 492 +/- 34-mu-l/min/g; T(Na) 91 +/- 3%. However, perfusion with both Eglin C and catalase completely prevented the toxic effects of LPS and FMLP-treated PMN on renal function. We conclude that in isolated kidneys, 1) the toxic effects of LPS requires FMLP-treated PMN and that 2) LPS and FMLP treated PMN cause progressive renal injury which is mediated by both O2 metabolites and neutrophil elastase.
引用
收藏
页码:618 / 623
页数:6
相关论文
共 38 条
  • [1] ROLES FOR THROMBOXANE-A-2 AND LEUKOTRIENES IN ENDOTOXIN INDUCED ACUTE-RENAL-FAILURE
    BADR, KF
    KELLEY, VE
    RENNKE, HG
    BRENNER, BM
    [J]. KIDNEY INTERNATIONAL, 1986, 30 (04) : 474 - 480
  • [2] O-2 METABOLITES AND NEUTROPHIL ELASTASE SYNERGISTICALLY CAUSE EDEMATOUS INJURY IN ISOLATED RAT LUNGS
    BAIRD, BR
    CHERONIS, JC
    SANDHAUS, RA
    BERGER, EM
    WHITE, CW
    REPINE, JE
    [J]. JOURNAL OF APPLIED PHYSIOLOGY, 1986, 61 (06) : 2224 - 2229
  • [3] PRODUCTION OF TUMOR NECROSIS FACTOR BY RAT MESANGIAL CELLS IN RESPONSE TO BACTERIAL LIPOPOLYSACCHARIDE
    BAUD, L
    OUDINET, JP
    BENS, M
    NOE, L
    PERALDI, MN
    RONDEAU, E
    ETIENNE, J
    ARDAILLOU, R
    [J]. KIDNEY INTERNATIONAL, 1989, 35 (05) : 1111 - 1118
  • [4] BEUTLER B, 1987, NEW ENGL J MED, V316, P379
  • [5] BORRIN BH, 1990, KIDNEY INT, V37, P1509
  • [6] INTERLEUKIN-1 DECREASES RENAL SODIUM-REABSORPTION - POSSIBLE MECHANISM OF ENDOTOXIN-INDUCED NATRIURESIS
    CAVERZASIO, J
    RIZZOLI, R
    DAYER, JM
    BONJOUR, JP
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1987, 252 (05): : F943 - F946
  • [7] DIRECT EFFECTS OF ENDOTOXIN ON THE FUNCTION OF THE ISOLATED PERFUSED RAT-KIDNEY
    COHEN, JJ
    BLACK, AJ
    WERTHEIM, SJ
    [J]. KIDNEY INTERNATIONAL, 1990, 37 (05) : 1219 - 1226
  • [8] CURRENT CONCEPTS - LYMPHOKINES
    DINARELLO, CA
    MIER, JW
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1987, 317 (15) : 940 - 945
  • [9] BACTERIAL LIPOPOLYSACCHARIDES PRIME HUMAN-NEUTROPHILS FOR ENHANCED PRODUCTION OF LEUKOTRIENE-B4
    DOERFLER, ME
    DANNER, RL
    SHELHAMER, JH
    PARRILLO, JE
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (03) : 970 - 977
  • [10] BACTERIAL LIPOPOLYSACCHARIDE ENHANCES CHEMOATTRACTANT-INDUCED ELASTASE SECRETION BY HUMAN-NEUTROPHILS
    FITTSCHEN, C
    SANDHAUS, RA
    WORTHEN, GS
    HENSON, PM
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 1988, 43 (06) : 547 - 556